Updated: July 2015
Updated: December 2010
Originally Posted: September 2004
Jennifer E. Fergeson, D.O.
Division of Allergy and Immunology,
University of South Florida Morsani College of Medicine
James A. Haley Veterans' Hospital
Tampa, FL 33612
Richard F. Lockey, M.D.
Distinguished University Health Professor
Professor of Medicine, Pediatrics and Public Health
Director, Division of Allergy and Immunology
Joy McCann Culverhouse Chair in Allergy and Immunology
University of South Florida Morsani College of Medicine
James A. Haley Veterans' Hospital
Michael A. Kaliner, MD FAAAAI
Medical Director, Institute for Asthma and Allergy
Chevy Chase and Wheaton, Maryland
Professor of Medicine, George Washington University School of Medicine
Richard F. Lockey, MD
Professor of Medicine, Pediatrics and Public Health
Director of the Division of Allergy and Immunology
Joy McCann Culverhouse Chair of Allergy and Immunology
University of South Florida College of Medicine and the James A. Haley Veterans' Hospital
Asthma exacerbations are avoidable with appropriate, regular therapy and patient education. Despite this, in the United States alone, approximately 12 million people each year experience an acute exacerbation of their asthma, a quarter of which require hospitalization .
An acute exacerbation of asthma should be correctly identified from poor asthma control. In acute asthma, patients will exhibit increasing shortness of breath, chest tightness, coughing, and/or wheezing. In contrast, poor asthma control typically presents with a diurnal variability in airflow and is a characteristic that is usually not seen during an acute exacerbation. Various clinical symptoms and signs may assist the clinician in determining the severity of acute asthma (Figure 1) [1,10].
To prevent severe exacerbations of asthma, the goals for the physician managing patients with asthma are:
1. Recognition of patients who are at a greater risk for near-fatal or fatal asthma.
2. Education of the patient to recognize a deterioration in their disease.
3. Provision of an individual action plan for the patient to manage the exacerbation and to know when to seek professional help.
4. Management of co-morbidities such as rhinitis, sinusitis, obesity, gastroesophageal reflux disease (GERD), obstructive sleep apnea (OSA), chronic obstructive respiratory disease (COPD), vocal cord dysfunction (VCD) and atopic dermatitis [2, 5-8].
Clinical estimates of severity based on an interview and a physical examination can result in an inaccurate estimation of disease severity; audible wheezing is usually a sign of moderate asthma, whereas no wheezing can be a sign of severe airflow obstruction. Symptoms of severe asthma include severe chest tightness, cough (with or without sputum), sensation of air hunger, inability to lie flat, insomnia and severe fatigue. The signs of severe asthma include use of accessory muscles of respiration, hyperinflation of the chest, tachypnea, tachycardia, sweating, diaphoresis, obtundation, apprehensive appearance, wheezing, inability to complete sentences and difficulty in lying down. Altered mental status, with or without cyanosis, is an ominous sign and immediate emergency care and hospitalization are required. A detailed examination should include examining for signs and symptoms of pneumonia, pneumothorax or a pneumomediastinum, the latter of which can be investigated by palpation for subcutaneous crepitations, particularly in the supraclavicular areas of the chest wall. Special attention should be paid to the patient's blood pressure, pulse and respiratory rate [1-4].
Differential Diagnosis of Acute Asthma
The differential diagnosis of acute asthma includes COPD, bronchitis, bronchiectasis, foreign body, extra-or intra-thoracic tracheal obstruction, cardiogenic pulmonary edema, non-cardiogenic pulmonary edema, pneumonia, pulmonary embolus, chemical pneumonitis, and hyperventilation syndrome [2-3].
Risk Factors for Acute Asthma
Particular risk factors for asthma exacerbations can be identified from the clinical history. The patient interview should include questions about recent events including [1,4]:
- Upper or lower respiratory tract infections
- Cessation or reduction of medication
- Concomitant medication, e.g., non-selective ß-blockers
- Allergen or pollutant exposure
Predictors of Fatal or Near Fatal Asthma
Major risk factors for near-fatal and fatal asthma are recognized, and their presence makes early recognition and treatment of an asthma exacerbation essential. The history should include a review of previous episodes of near-fatal asthma and whether the patient has experienced multiple emergency room visits or hospitalizations, particularly those requiring admission to an intensive care unit, involving respiratory failure, intubation and mechanical ventilation. A history of allergic asthma and other known or suspected allergic symptoms should be obtained. For example, Nelson et al. identified a trigger for severe asthma is allergy to the mold Alternaria and several dust mite species [4,9].
Compliance with medical treatments should be reviewed; poor compliance with prescribed therapies is a major risk factor. Inadequate therapy may include excessive use of ß2-agonists, concomitant use of ß-blockers, and failure to prescribe or use inhaled corticosteroids (ICS) as a primary therapy. Recent withdrawal of oral corticosteroids (OCS) suggests that the patient is at greater risk for a severe exacerbation. Limited access of the patient to appropriate health care and lack of education about appropriate management strategies are additional risk factors. Socioeconomic factors associated with severe asthma exacerbations include the non-compliant adolescent or elderly asthmatics living in inner city environments. Certain ethnic groups within a population may have a higher incidence of severe asthma [4,11].
Serial measurements of lung function facilitate quantification of the severity of airflow obstruction and response to therapy. A peak expiratory flow (PEF) rate provides a simple, quick, and cost effective assessment of the severity of airflow obstruction. While standing, the patient takes a deep breath to maximum inspiration, briefly holds the breath, and with lips sealed around a mouthpiece blows out as hard and fast as possible. The best of three recordings is logged as the PEF and compared to predicted normal values based on gender, age and height or to previous determinations. Patients can be supplied with an inexpensive PEF meter and taught to perform measurements at home to detect deterioration of their asthma. An individual management plan will be based upon the personal best PEF value, and pre-determined PEF values can be set at which time the patient is alerted to the degree of severity of symptoms and can institute appropriate therapy and/or consult their physician (Figure 2). In non-acute settings, assessment of PEF and spirometry before and after administration of a bronchodilator can indicate the likely degree of improvement in lung function which can be achieved by adequate therapy. PEF values of 50-79% of predicted or personal best signify need for immediate treatment with an inhaled short acting beta agonist (SABA), PEF values below 50% indicate the need for immediate medical care, and PEF values below 35% indicates a severe life threatening episode. Initial treatment with a SABA via nebulizer or metered dose inhaler (MDI) should be administered as 4-8 puffs every 20 minutes for up to 1 hour and then as needed every 1-4 hours. Response to the SABA and further management is depicted in Figure 2 [1, 11-14].
The forced expiratory volume in one second (FEV1) is measured by spirometry to assess the volume of air exhaled over time and is the most sensitive test for airflow obstruction. FEV1 is less variable than PEF and is independent of effort once a moderate effort has been made by the patient. While sitting, the patient is asked to forcibly exhale from the point of maximal inhalation into the spirometer, ideally over 6 seconds. Three determinations should be obtained, if possible, with the best being recorded, and severity of assessment is made by comparison to predicted normal values for the gender, height and age of the patient or to a previous value. Post bronchodilator reversibility should be assessed and an increase in FEV1 > 12% (minimum > 200 ml) is diagnostic of asthma [1, 11].
Chest radiographs are not usually necessary for the diagnosis of acute asthma if the examination of the chest reveals no abnormal findings other than the expected clinical signs and symptoms associated with an acute exacerbation of asthma. If a complication is suspected, such as pneumonia, pneumothorax, pneumomediastinum, or atelectasis secondary to mucous plugging, a chest X-ray should be obtained .
Arterial blood gas analysis should be reserved for patients with oxygen saturations < 92% or those who do not respond to intensive conventional treatment with an FEV1 < 30%. Proper interpretation of the pH, PaO2, and PaCO2 may help further assess the severity of an acute exacerbation of asthma (Figure 1). For example, a breathless asthmatic presenting with a PaCO2 > 45 mmHg indicates a life threatening attack and the need for transfer to a medical intensive care unit for further care. Less than 10% of asthmatic patients presenting to the emergency department are found to have arterial oxygen values < 50 mmHg and carbon dioxide levels > 45 mmHg [11, 15].
Figure 1. Acute asthma severity: clinical signs and symptoms. Originally published as Figure 5-3 in the Expert Panel Report 3.
Figure 2. Management of Asthma Exacerbations: Home Treatment Predicted. Originally published as Figure 5-4 in the Expert Panel Report 3.
Treatment is based not only on assessment of lung function parameters but on clinical findings and the efficacy of previous treatment. A seasonal exacerbation of asthma in a pollen-sensitive patient is more easily treatable than an exacerbation triggered by a viral infection. Allergic asthma is more likely to respond immediately to inhaled ß2-agonist therapy and to an adjustment in inhaled corticosteroids, whereas the infected patient is more likely to require a systemic corticosteroid (SCS). A patient who is over-using short-acting ß2-agonists may be refractory to nebulized ß2-agonists and will usually require a systemic corticosteroid. Physician knowledge of an individual patient will suggest whether a systemic corticosteroid is required or whether an exacerbation can be managed on very high doses of inhaled corticosteroids [3,11,16].
Recommended treatment choices in order of introduction in the acute setting are listed below and depicted in Table 3.
Primary treatment choices include:
- SABA; inhaled by MDI or by nebulization
- Anticholinergics; inhaled by MDI or nebulization
- Corticosteroids; parenteral, oral or inhaled
Secondary treatment choices may include:
- Epinephrine; Intramuscular (IM) or subcutaneous (SQ)
- Magnesium sulfate; parenteral
- Heliox – driven albuterol
- Intubation and mechanical ventilation
Figure 3. Acute Asthma Management: Emergency Department and Hospital-Based Care. Originally published as Fig 5-6 in the Expert Panel Review 3.
The Expert Panel Report 3 (EPR3) guidelines recommend the use of only selective SABAs in high doses (i.e. albuterol, levalbuterol) due to the risk of cardiotoxicity, especially in elderly asthmatic patients. Initial treatment should begin with albuterol, either administered by MDI with a spacer device or mask (children < 4 years of age) or nebulizer.
In children, albuterol by MDI is given at a dose of 90 µg/puff, 4-8 puffs every 20 minutes for 3 doses and then every 1-4 hours as needed. Nebulized albuterol is given at a dose of 0.15 mg/kg (minimum dose 2.5 mg) every 20 minutes for up to 3 doses and then 0.15-0.3 mg/kg up to 10 mg every 1-4 hours as needed .
In adults, albuterol by MDI is given at a dose of 90µg/puff, 4-8 puffs every 20 minutes for up to 4 hours and then every 1-4 hours as needed. Nebulized albuterol is administered at a dose of 2.5-5.0 mg every 20 minutes for up to 3 doses and then 2.5-10 mg every 1-4 hours as needed.
Treatment should be continued until the patient has stabilized or a decision to hospitalize is made. Studies show that the use of either MDI or nebulizer for delivery of inhaled SABAs produces similar outcomes. Nebulizer treatment may be preferred in patients who are unable to cooperate effectively using an MDI because of the severity of acute asthma, age or agitation. Additionally, continuous nebulization should be considered in very severe asthma exacerbations based on evidence of reduced admissions and improved pulmonary function [11, 17-19].
Levalbuterol (R-albuterol) nebulizer solution can be given in a similar fashion and at doses ranging from 0.63 mg/3ml to 1.25 mg/0.5ml as needed. Notably, levalbuterol administered at one-half the mg dose of albuterol is found to deliver comparable efficacy and safety. However, the efficacy of continuous nebulization has not been evaluated .
In children, levalbuterol by MDI is given at a dose of 45 µg/puff, 4-8 puffs every 20 minutes for 3 doses and then every 1-4 hours as needed. Nebulized levalbuterol is given at a dose of 0.075 mg/kg (minimum dose 1.25mg) every 20 minutes for up to 3 doses and then 0.075-0.15 mg/kg up to 5 mg every 1-4 hours as needed .
In adults, levalbuterol by MDI is given at a dose of 45 µg/puff, 4-8 puffs every 20 minutes for up to 4 hours and then every 1-4 hours as needed. Nebulized levalbuterol is given at a dose of 1.25-2.5 mg every 20 minutes for up to 3 doses and then 1.25mg-5mg every 1-4 hours as needed .
Continuous administration of albuterol via large volume nebulizers may be more efficacious when compared to intermittent administration in patients with severe asthma exacerbations. Continuous administration of nebulized albuterol should be given at a dose of 0.5 mg/kg/hour in children and 10-15mg/hour in adults .
For patients unable or unwilling to use an MDI/spacer or nebulizer, epinephrine (1:1000, 1mg/ml) injected subcutaneously or intramuscularly into the arm in children at a dose of 0.01 mg/kg (maximum dose 0.5 mg) and in adults 0.3-0.5 mg, every 20 minutes for up to 3 doses, as long as the patient is carefully monitored for signs of adrenergic toxicity. At this time, there is no proven advantage of use of systemic therapy over aerosol treatment. If there is no immediate response to epinephrine treatment should be discontinued and the patient hospitalized .
Ipratropium bromide is a quaternary derivative of atropine sulfate available as a nebulizer solution. It provides competitive inhibition of acetylcholine at the muscarinic cholinergic receptor, thus relaxing smooth muscle in large central airways. It is not a first line therapy, but can be added in severe asthma particularly when albuterol is not optimally beneficial. It can be given with albuterol or levalbuterol and may be used for up to 3 hours in the initial management of acute asthma. There is increasing support for adding ipratropium bromide to β2-agonist therapy in more severe asthma exacerbations in children. Studies indicate that combined therapy reduces the risk of hospital admission by 25% [11, 19-20].
Ipratropium bromide may be administered by nebulizer to children at a dose of 0.25-0.5 mg and in adults 0.5 mg, every 20 minutes for up to 3 doses, and then every hour as needed. Administration via MDI (spacer and mask in children < 4 years of age) can be given at a dose of 18 µg/puff for adults and children. Children should receive 4-8 puffs and adults 8 puffs, every 20 minutes for up to 3 doses, and then continued as needed for up to 3 hours .
There are no substantial data for the immediate usefulness of corticosteroids in the acute setting because effectiveness of action is not seen for hours after administration. However, oral corticosteroids (OCS) are the best medications available to reduce airway inflammation and should be used immediately and until the attack has abated as evidenced by the PEF and FEV1 returning to near baseline levels and the patient becoming asymptomatic .
High dose ICS may be initiated in selected patients. Current evidence suggests equivalence in treatment of mild asthma exacerbations with oral corticosteroids. However, due to limited data, high dose ICS should be reserved for patients with mild asthma and those who refuse or cannot tolerate OCS, e.g., have brittle diabetes or experience major side effects. Current guidelines recommend at least quadrupling the recommended dose of ICS. For example, a top recommended maintenance dose of fluticasone may be increased from 220 µg, 2 puffs, 2x/day to 220 µg, 4 puffs, 4x/day for exacerbations. Treatment should be started before the patient becomes too ill to manage their disease at home. Inhaled therapy reduces the risk of unwanted effects associated with oral corticosteroid treatment, e.g., insomnia, increased appetite, hyperactivity, psychosis, and effects on bone metabolism and other organ systems. ICS are less likely to be effective in patients with upper respiratory tract infections exacerbating their asthma or those who are over-using ß2-agonists. When an ICS is not utilized, a systemic glucocorticoid with instructions for its use should be prescribed as a back up treatment regimen and the patient and/or family should understand when to start it and also have immediate access to a physician and/or other healthcare professional until the asthma exacerbation is resolved [21-23].
Short courses of OCS are effective to establish control of flare-ups of asthma or during a period of gradual deterioration of asthma not responding to increased doses of an inhaled corticosteroid. Prednisone or its equivalent should be administered in children at a dose of 1-2 mg/kg (maximum 60 mg/day) given in 2 divided doses for 3-10 days and in adults 40 to 80 mg/day given in 2 divided doses for 5-10 days or until the PEF reaches 70% of predicted or personal best. Higher doses result in increased side effects and no appreciable increased therapeutic benefit [11, 23].
Treatment should be continued until the patient is well or achieves a PEF of 80% of personal predicted best. Improvement may be seen between 5 to 14 days, although patients whose asthma is corticosteroid-resistant may take weeks to show a response. It is not necessary to taper OCS after a course of less than three weeks, but after use for longer than 3 weeks, it is advisable to taper the medication over one to two weeks to decrease withdrawal side effects such as adrenal insufficiency, fatigue, myalgias and joint pain [11,23].
Intramuscular (IM) or intravenous (IV) corticosteroids may be used in the initial treatment of acute asthma, but there is no evidence that giving corticosteroids IM or IV results in a more rapid onset of action than oral administration. The recommended dose for IV methylprednisolone is 1 to 2 mg/kg for 24 hours in divided doses .
Poorly controlled asthmatics treated with intermittent or continuous OCS or high-dose ICS pose the greatest risk for the development of osteoporosis. However, the effect of ICS on bone metabolism and subsequent osteoporosis still remains controversial. The American College of Rheumatology recommends that patients initiating treatment with OCS should be screened for osteoporotic fracture risk, lifestyle modifications, and potential treatment with a bisphosphonate. The Fracture Risk Assessment Tool (FRAX) may be used to calculate the risk of a major osteoporotic bone fracture and assists in categorizing these patients into one of three groups: low, medium, or high risk. Initiation of bisphosphonate treatment is recommended for postmenopausal women and men > 50 years of age who are categorized as low risk and taking prednisone or it’s equivalent of > 7.5 mg/day for > 3 months or longer. In this same group, those categorized as medium risk should begin bisphosphonate treatment if they are taking any dose of prednisone or it’s equivalent for > 3 months. Patients identified as high risk should begin treatment with a bisphosphonate regardless of the dose or duration of treatment with prednisone or it’s equivalent .
The quantitative risks of oral corticosteroid related adverse events (AE) was evaluated by Ledford et al. in a retrospective cohort study. Results demonstrat
ed that an increase in cumulative SCS exposure is associated with an increased risk for AE including diabetes mellitus, skeletal conditions (osteoporosis, fractures), mania, depression, opportunistic infections, pneumonia, hypertension, and lipid disorders, with the highest risk associated with skeletal conditions and infections. The adjusted risk for developing AE is 7% per additional 1 gram equivalent prednisone exposure .
Magnesium sulfate has both immediate bronchodilator effects and mild anti-inflammatory effects. Several systematic reviews conclude that IV magnesium is a safe and effective treatment and may be considered in patients presenting with severe life threatening asthma exacerbations (FEV1 < 25% predicted) and those who remain in the severe category after 1 hour of intensive conventional treatment. The recommended dose is 2 gm IV over 20 min in adults and 25-75 mg/kg in children (maximum dose of 2 gm) [1,11].
Heliox – Driven Albuterol
The role of heliox - driven albuterol in the treatment of acute exacerbations continues to be a controversial topic. Many limitations remain that complicate the understanding of the current literature. Despite these uncertainties, heliox – driven albuterol should be considered in both children and adults who exhibit severe life-threatening exacerbations and those who remain in the severe category after 1 hour of intensive conventional therapy [11,24].
Failure to respond to treatment necessitates hospitalization. The patient’s fluid status should be assessed and oral or intravenous hydration therapy administered as indicated. Hydration in young infants and children may be essential as these patients are at increased risk for dehydration due to poor oral intake and an increased respiratory rate. Oxygen may be administered at 2 to 4 L/min via a nasal cannula or mask, whichever is better tolerated to maintain a SaO2 > 90%. In pregnant patients and patients with underlying cardiac disease, a SaO2 > 95% is recommended. The patient should be monitored continuously with pulse oximetry and telemetry. Blood gases should be obtained until the patient is stable. The patient should be treated with continuous nebulized albuterol or levalbuterol, with or without ipratropium bromide, and a corticosteroid, e.g., methylprednisolone, or its equivalent, 1-2 mg/kg in divided doses every 24 hours. If the patient is not responding and is deteriorating a decision should be made to assist ventilation before the patient has a respiratory arrest. Indicators of imminent respiratory failure include worsening or persistent hypercapnia, depressed mental status, and/or exhaustion. Viral respiratory tract infections are more common in acute asthma exacerbation and therefore antibiotics should be reserved for patients who present with evidence of a co-existing bacterial infection, i.e., pneumonia, bronchitis, sinusitis. The EPR3 does not recommend the use of methylxanthines, mucolytics, sedation or chest physiotherapy for treatment in acute asthma [1, 11,25].
Patient education is important to ensure that the patient understands that asthma is mostly a chronic disease and necessitates the avoidance of allergens, prevention of infections, compliance with routine vaccinations, management of comorbid conditions and adherence to treatment regimens. The importance of taking an ICS on a regular basis and limiting bronchodilator use cannot be over emphasized. An individual management plan should include how to recognize an impending exacerbation and provide an incremental therapy regimen to be implemented according to the degree of severity and when to seek medical care. A routine measurement of PEF can sometimes help patients better assess the severity of their asthma [1,25-26].
After discharge from the hospital, approximately 10-20% of patients treated for acute asthma will relapse within 2 weeks of discharge. This may be due to unresolved inflammation causing continued airway sensitivity to inhaled irritants. As a result, the EPR3 strongly encourages treatment with systemic corticosteroids following emergency room discharge. Alternatively, as mentioned earlier, treatment with high dose ICS (quadruple the ICS dose) can be considered in patients with underlying mild asthma or those who cannot tolerate an oral corticosteroid. Upon completion of OCS treatment, ICS therapy should be resumed or initiation of short/long term ICS therapy considered to reduce acute asthma exacerbations and subsequent emergency room visits. The ICS dose should eventually be reduced incrementally to maintain a PEF at a personal best level. A combination of long acting β2-agonist and an ICS can be considered in order to achieve the lowest dose possible [11,25-27].
The patient should be evaluated for allergy with skin prick/puncture tests or serum testing for IgE-sensitization and allergen avoidance strategies discussed if the clinical history suggests that allergen contact may have precipitated the asthma exacerbation. Compliance with prescribed therapy should be reviewed, and the patient's technique in using MDI should be routinely checked. Contact with tobacco, drugs, irritants and fumes which may precipitate an attack should be considered and the patient advised how to avoid contact with such agents. Social factors and psychiatric disorders need to be appropriately treated because each can affect access to care, adherence, and lead to other comorbid conditions [1,4,11].
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